C-FGF23 peptide alleviates hypoferremia during acute inflammation

Area of Science:

• Immunology
• Endocrinology
• Hematology

Background:

• Hypoferremia, characterized by low serum iron, is an acute phase response to infection and inflammation, limiting pathogen access to iron.
• Toll-like receptor (TLR) activation, a key innate immune response, induces hypoferremia primarily via increased hepcidin, an iron hormone.
• Erythropoiesis stimulates hepcidin suppression through erythroferrone, while iron deficiency upregulates osteocyte-secreted FGF23.

Purpose of the Study:

• To investigate the hypothesis that FGF23 induction contributes to TLR4-mediated hypoferremia.
• To determine if impairing FGF23 signaling can alleviate lipopolysaccharide (LPS)-induced hypoferremia.

Main Methods:

• Utilized wild-type mice and the C-terminal tail of FGF23 to inhibit endogenous FGF23 signaling.
• Administered LPS (a TLR4 agonist) to induce hypoferremia and assessed its impact on iron metabolism and related hormones.
• Measured serum iron, transferrin saturation, hepcidin, erythropoietin (Epo), and FGF23 levels.

Main Results:

• LPS induced FGF23 expression early, preceding hepcidin upregulation and Epo downregulation, leading to decreased serum iron and transferrin saturation.
• Disruption of FGF23 signaling significantly reduced LPS-induced hepatic and circulating hepcidin levels.
• FGF23 inhibition abrogated LPS-induced iron sequestration in the liver and spleen, alleviating hypoferremia.

Conclusions:

• FGF23 is induced by TLR4 activation and contributes significantly to acute hypoferremia.
• Inhibition of FGF23 signaling represents a novel therapeutic strategy to alleviate LPS-induced acute hypoferremia and restore iron homeostasis.